Hepatocellular carcinoma (HCC) is increasing in frequency in the United States. The age-adjusted incidence rates have doubled over the past 2 decades. Similar increases have affected the mortality and hospitalization rates. Although there has been a small recent improvement in survival, it remains generally dismal (median, 8 months). It is estimated that 8500 to 11,500 new cases of HCC occur annually in the United States. There are striking differences in the incidence of HCC related to age, gender, race, and geographic region. Although it remains an affliction of the elderly (mean age, 65 years) population, there has been a shift toward relatively younger age cases. Men are affected 3 times more frequently than women, Asians are affected 2 times more than blacks, and Hispanics are affected 2 times more often than whites. However, the recent increase has disproportionately affected white (and Hispanic) men between ages 45 and 65 years. The temporal changes of risk factors among HCC cases in the United States remain unclear. However, available studies indicate that hepatitis C virus (HCV) infection acquired 2-4 decades ago explains at least half of the observed increase in HCC; HCV-related HCC is likely to continue to increase for the next decade. A variable but significant proportion of cases (15% to 50%) do not have evidence of the risk factors of viral hepatitis or heavy alcohol consumption. The insulin resistance syndrome, manifesting as obesity and diabetes, is emerging as a risk factor for HCC in the United States; however, its impact on the current trend in HCC remains unclear.